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Review
. 2018 Oct 29;8(4):75.
doi: 10.3390/diagnostics8040075.

Liquid Biopsy in Gastrointestinal Cancers

Aman Saini  1 , Yash Pershad  2 , Hassan Albadawi  3 , Malia Kuo  4 , Sadeer Alzubaidi  5 , Sailendra Naidu  6 , M-Grace Knuttinen  7 , Rahmi Oklu  8
Affiliations
Review

Liquid Biopsy in Gastrointestinal Cancers

Aman Saini et al. Diagnostics (Basel). .

Abstract

Liquid biopsy is the sampling of any biological fluid in an effort to enrich and analyze a tumor's genetic material. Peripheral blood remains the most studied liquid biopsy material, with circulating tumor cells (CTC's) and circulating tumor DNA (ctDNA) allowing the examination and longitudinal monitoring of a tumors genetic landscape. With applications in cancer screening, prognostic stratification, therapy selection and disease surveillance, liquid biopsy represents an exciting new paradigm in the field of cancer diagnostics and offers a less invasive and more comprehensive alternative to conventional tissue biopsy. Here, we examine liquid biopsies in gastrointestinal cancers, specifically colorectal, gastric, and pancreatic cancers, with an emphasis on applications in diagnostics, prognostics and therapeutics.

Keywords: circulating tumor DNA; circulating tumor cells; gastrointestinal cancer; liquid biopsy.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Sources of liquid biopsy material. A variety of biologic fluids can contain tumor-derived genetic material. In addition to blood, these fluids can include cerebrospinal fluid (CSF), saliva, pleural effusions, and urine. ctDNA and CTC’s can be extracted from this fluid and genetic alterations including point mutations, methylation changes, and gene fusions can be analyzed. Reproduced with permission from [2]; published by Springer Nature Limited, 2017.
Figure 2
Figure 2
Detection of CTC’s using microfluidics. (a) Diagram of CTC isolation using microfluidic chips. (b) Immunofluorescent staining of CTC’s. (c) CT scan of liver (top) with 3D reconstruction (bottom) demonstrating high and low tumor volume (TV) (d) CTC’s/mL of blood in healthy donors (HD) versus patients with high and low TV. Bar = median. * p = 0.045. (e) Scatter plot demonstrating tumor volume (cc) versus CTC’s/mL. Spearman r = 0.3043. Reproduced under open access [16].
Figure 3
Figure 3
Liquid biopsy can non-invasively assess the molecular heterogeneity of cancers. CTC’s, ctDNA, ctRNA, and exosomes can be used to characterize the heterogeneity of distinct tumor lesions with different genetic mutations or alterations. The tables demonstrate the detection of point mutations in various genes through candidate-gene or next-generation sequencing analysis. The fluorescence micrograph demonstrates the use of fluorescence in situ hybridization analysis to detect copy-number variations. Reproduced with permission from [2]; published by Springer Nature Limited, 2017.
Figure 4
Figure 4
Serial liquid biopsies to monitor therapeutic response and treatment resistance. Hypothetical diagram of a patient with metastatic breast cancer. First- and second-line treatments are based upon tissue biopsy which does not completely assess the heterogeneity of metastatic disease, nor does it account for treatment resistance over time. Serial liquid biopsies could help to characterize tumor heterogeneity, detect treatment resistance and disease progression before it becomes apparent clinically. Reproduced with permission from [58].
See this image and copyright information in PMC

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